Cyclic peptide for treating cancer

Abstract

The present disclosure generally relates to a circularized peptide for treating cancer. An cyclic peptide is disclosed that has an amino acid sequence selected from Lys-X 5 -Glu-X 1 -X 2 -Gln-Met-Glu-Asp-Asp-X 3 -X 4 (SEQ ID NO: 3), X 10 -Gly-Glu-Val-Leu-X 11 -Met-Glu-Asp-Asp-Leu-Val (SEQ ID NO: 4), Lys-Gly-X 6 -Val-Leu-Gln-Met-X 7 -X 8 -X 9 -Leu-Val (SEQ ID NO: 5), Lys-X 5 -Glu-X 1 -X 2 -Gln-X 12 -Glu-Asp-Asp-X 3 -X 4 (SEQ ID NO: 9), and X 10 -X 5 -X 6 -Val-Leu-Gln-Met-Glu-Asp-X 9 -X 3 -X 4 (SEQ ID NO: 10). The amino acids X 1 , X 2 , X 3 , and X 4 can be each independently valine, leucine, isoleucine, or alanine; X 5 can be glycine, alanine, leucine, isoleucine, or valine; X 6 , X 7 , X 8 , and X 9 can be each independently glutamic acid or asparagine; X 10 can be lysine or arginine; X 11 can be methionine or cysteine; and X 12 can be methionine or norleucine. The cyclic peptide can have the amino acid sequence Lys-Gly-Glu-Val-Leu-Gln-Met-Glu-Asp-Asp-Leu-Val (SEQ ID NO: 1).

What is claimed is: 
     
       1. A cyclic peptide selected from the group consisting of:
 the amino acid sequence consisting of SEQ ID NO: 3 (Lys-X 5 -Glu-X 1 -X 2 -Gln-Met-Glu-Asp-Asp-X 3 -X 4 ), wherein X 5  is glycine, alanine, leucine, isoleucine, or valine, X 1  is valine, X 2  is leucine, and X 3  and X 4  are each independently valine, leucine, isoleucine, or alanine; 
 the amino acid sequence consisting of SEQ ID NO: 4 (X 10 -Gly-Glu-Val-Leu-X 11 -Met-Glu-Asp-Asp-Leu-Val), wherein X 10  is lysine or arginine, and X 11  is glutamine; 
 the amino acid sequence consisting of SEQ ID NO: 5 (Lys-Gly-X 6 -Val-Leu-Gln-Met-X 7 -X 8 -X 9 -Leu-Val), wherein X 6  and X 7  are each independently glutamic acid, and X 8  and X 9  are each independently glutamic acid or aspartic acid; 
 the amino acid sequence consisting of SEQ ID NO: 9 (Lys-X 5 -Glu-X 1 -X 2 -Gln-X 12 -Glu-Asp-Asp-X 3 -X 4 ), wherein X 5  is glycine, alanine, leucine, isoleucine, or valine, X 1  is valine, X 2  is leucine, X 12  is methionine or norleucine, and X 3  and X 4  are each independently valine, leucine, isoleucine, or alanine; and 
 the amino acid sequence consisting of SEQ ID NO:  10  (X 10 -X 5 -X 6 -Val-Leu-Gln-Met-Glu-Asp-X 9 -X 3 -X 4 ), wherein X 10  is lysine or arginine, X 5  is glycine, alanine, leucine, isoleucine, or valine, X 6  is glutamic acid, X 9  is glutamic acid or aspartic acid, NS X 3  and X 4  are each independently valine, leucine, isoleucine, or alanine, 
 and wherein the cyclic peptide is circularized by forming an amide bond between the N-terminal amino acid and the C-terminal amino acid. 
 
     
     
       2. The cyclic peptide of  claim 1 , wherein the amino acid sequence is SEQ ID NO: 3. 
     
     
       3. The cyclic peptide of  claim 1 , wherein the peptide consists of the amino acid sequence Lys-Gly-Glu-X 1 -X 2 -Gln-Met-Glu-Asp-Asp-X 3 -X 4  (SEQ ID NO: 2). 
     
     
       4. The cyclic peptide of  claim 1 , wherein the amino acid sequence is SEQ ID NO: 4. 
     
     
       5. The cyclic peptide of  claim 1 , wherein the amino acid sequence is SEQ ID NO: 5. 
     
     
       6. The cyclic peptide of  claim 1 , wherein the peptide is labeled with a detectable label. 
     
     
       7. The cyclic peptide of  claim 1 , wherein the peptide is conjugated to a cytotoxic molecule, a radioactive molecule, or a hydrophobic group. 
     
     
       8. A composition comprising a pharmaceutically acceptable carrier and the cyclic peptide of  claim 1 . 
     
     
       9. A method of inhibiting helicase function comprising contacting a cell with a helicase-inhibiting amount of the cyclic peptide of  claim 1 . 
     
     
       10. A method of treating cancer comprising administering to a subject having the cancer with a therapeutically effective amount of a cyclic peptide selected from the group consisting of:
 the amino acid sequence consisting of SEQ ID NO: 3 (Lys-X 5 -Glu-X 1 -X 2 -Gln-Met-Glu-Asp-Asp-X 3 -X 4 ), wherein X 5  is glycine, alanine, leucine, isoleucine, or valine, X 1  is valine, X 2  is leucine, and X 3  and X 4  are each independently valine, leucine, isoleucine, or alanine; 
 the amino acid sequence consisting of SEQ ID NO: 4 (X 10 -Gly-Glu-Val-Leu-X 11 -Met-Glu-Asp-Asp-Leu-Val), wherein X 10  is lysine or arginine, and X 11  is glutamine; 
 the amino acid sequence consisting of SEQ ID NO: 5 (Lys-Gly-X 6 -Val-Leu-Gln-Met-X 7 -X 8 -X 9 -Leu-Val), wherein X 6  and X 7  are each independently glutamic acid, and X 8  and X 9  are each independently glutamic acid or aspartic acid; 
 the amino acid sequence consisting of SEQ ID NO: 9 (Lys-X 5 -Glu-X 1 -X 2 -Gln-X 12 -Glu-Asp-Asp-X 3 -X 4 ), wherein X 5  is glycine, alanine, leucine, isoleucine, or valine, X 1  is valine, X 2  is leucine, X 12  is methionine or norleucine, and X 3  and X 4  are each independently valine, leucine, isoleucine, or alanine; and 
 the amino acid sequence consisting of SEQ ID NO: 10 (X 10 -X 5 -X 6 -Val-Leu-Gln-Met-Glu-Asp-X 9 -X 3 -X 4 ), wherein X 10  is lysine or arginine, X 5  is glycine, alanine, leucine, isoleucine, or valine, X 6  is glutamic acid, X 9  is glutamic acid or aspartic acid, NS X 3  and X 4  are each independently valine, leucine, isoleucine, or alanine, 
 wherein the cyclic peptide is circularized by forming an amide bond between the N-terminal amino acid and the C-terminal amino acid, and 
 wherein the cancer is selected from lung carcinoma, liver carcinoma, testicular cancer, pancreatic carcinoma, brain glioma, pancreatic ductal adenocarcinoma, colorectal carcinoma, osteosarcoma, cervical cancer, or breast cancer. 
 
     
     
       11. The method of  claim 10 , wherein the amino acid sequence is SEQ ID NO: 3. 
     
     
       12. The method of  claim 10 , wherein the cancer is lung cancer, liver cancer, or brain cancer. 
     
     
       13. The method of  claim 10 , wherein the cyclic peptide is administered via a route selected from the group consisting of oral administration, nasal administration, administration by inhalation, rectal administration, intraperitoneal injection, intravascular injection, subcutaneous injection, transcutaneous administration, and intramuscular injection. 
     
     
       14. The method of  claim 10 , further comprising administering a chemotherapeutic agent. 
     
     
       15. A kit comprising: a container containing the cyclic peptide of  claim 1 ; and instructional materials teaching the use of the peptide for carrying out a method selected from the group consisting of  claim 9 and claim 10 .